Nitric Oxide Donor Isosorbide Mononitrate Research Articles

Evaluating the efficacy of outpatient use of isosorbide mononitrate on cervical ripening in pregnant women with unfavourable cervix

The aim of the present study was to evaluate the efficacy of outpatient administration of nitric oxide donor isosorbide mononitrate for cervical ripening. A randomised clinical trial was performed on term pregnant women with Bishop Score < 6. In the case group, Isosorbide-5-mononitrate capsule and in the control group, placebo was inserted in the posterior vaginal fornix for two consecutive days. The main outcomes were increases in Bishop Score after 48 hours of intervention, number of vaginal deliveries and interval from intervention to delivery. There was a significant increase of the mean Bishop score in the isosorbide group [3.57 ± 1.12 VS 1.54 ± 1.42 respectively (p = .001)]. The other outcome variables did not show a significant difference between the two groups except for headache which was significantly more in the case group. No cases of tachysystole were observed in the two groups. Additionally, haemoglobin levels after delivery did not show a significant difference between the two groups. Impact statement: What is already known on this subject? Cervical ripening in women with an unfavourable cervix and having an indication for induction of labour is an important issue in modern obstetrics. Different methods have been used for cervical ripening and induction of labour including mechanical (i.e. laminaria tents, Dilapan-S, foley catheter), medical (i.e. PGs) and supportive methods. There is no consensus on the best option for cervical ripening What will the results of this study add to the current knowledge of this subject? Outpatient administration of nitric oxide could affect cervical ripening without a significant improvement in the duration of different stages of labour, intervention to delivery interval and number of vaginal deliveries. What are the implications of these findings for clinical practice and/or further research? Due to the contradictory results of various studies, more studies should be performed with greater sample size to evaluate nitric oxide donor isosorbide mononitrate effect on labour duration and reducing caesarean deliveries. Additional data is needed to assess the real impact of NO donors on different stages of labour and its implications.

Use of Nitric Oxide Donor Isosorbide Mononitrate for Cervical Ripening at 41 Weeks’ Gestation

Background: The ideal agent for cervical ripening would induce adequate cervical ripening with minimal adverse effects to the mother and the fetus; the most favorable method for cervical ripening is not fully agreed till now; however, vaginal administration of isosorbide mononitrate (IMN) is considered a low-risk method of labor induction for post term. Our study was designed to assess the effect of IMN on cervical ripening and labor induction among 41 weeks pregnant women. Objectives: To assess the efficacy of the nitric oxide donor isosorbide mononitrate on cervical ripening at 41 weeks gestation. Materials and Methods: This study was conducted on 100 pregnant women recruited from the outpatient clinic fulfilling the inclusion criteria. Cases were divided into 2 groups. In first group 40 mg isosorbide mononitrate (IMN) tablet was applied vaginally in posterior fornix, and in second group placebo was applied vaginally in posterior fornix. Following up the cervical status after 24 hours of administration, the patient were asked about new symptoms especially headache, palpitation, dizziness or abdominal pain and the mode of delivery was assessed. Results: There was a significant improvement in the bishop score in the first group rather than the placebo group. No significant difference between the two groups was as regards the mode of delivery. Conclusion: IMN may be used for cervical preparation only before induction of labor in post term cases.

Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice.

Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H2O2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.

Outpatient cervical ripening by nitric oxide donors for prolonged pregnancy: a randomized controlled trial.

To assess whether outpatient cervical ripening at 41 0/7 weeks of gestation with the nitric oxide donor isosorbide mononitrate reduces cesarean delivery rates in nulliparous women with an unfavorable cervix. We recruited nulliparous pregnant women with a Bishop score less than 6 in a randomized, multicenter, double-blind, placebo-controlled trial. Women received 40 mg vaginal isosorbide mononitrate or a placebo at 41 0/7, 41 2/7, and 41 4/7 weeks of gestation. They returned home between visits. At 41 5/7 weeks of gestation, for women who had not yet given birth, labor was induced with oxytocin or prostaglandins, depending on cervical status. We needed 685 women per group to detect a 25% reduction in the cesarean delivery rate, the primary outcome measure, from 25% in the placebo group to 18.75% in the isosorbide mononitrate group (1-β=0.8, α=0.05, two-sided). The NOCETER (NO donors for reduction of CEsareans at TERm) trial was a negative study. The cesarean delivery rate was 27.3% (185/678) in the isosorbide mononitrate group and 27.2% (186/684) in the placebo group (relative risk 1.00, 95% confidence interval [CI] 0.84-1.19). None of the maternal secondary efficacy outcomes differed between groups. Side effects were more common among women receiving isosorbide mononitrate than in the placebo group (78.8% [534/678] compared with 27.9% [191/684], relative risk 2.82, 95% CI 2.49-3.20). Composite perinatal morbidity did not differ between groups. Outpatient cervical ripening with vaginal isosorbide mononitrate for prolonged pregnancy in nulliparous women does not reduce cesarean delivery rate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00930618.

Liposome-Encapsulated ISMN: A Novel Nitric Oxide-Based Therapeutic Agent against Staphylococcus aureus Biofilms

Background Staphylococcus aureus in its biofilm form has been associated with recalcitrant chronic rhinosinusitis with significant resistance to conventional therapies. This study aims to determine if liposomal-encapsulation of a precursor of the naturally occurring antimicrobial nitric oxide (NO) enhances its desired anti-biofilm effects against S. aureus, in the hope that improving its efficacy can provide an effective topical agent for future clinical use.Methodology S. aureus ATCC 25923 biofilms were grown in-vitro using the Minimum Biofilm Eradication Concentration (MBEC) device and exposed to 3 and 60 mg/mL of the NO donor isosorbide mononitrate (ISMN) encapsulated into different anionic liposomal formulations based on particle size (unilamellar ULV, multilamellar MLV) and lipid content (5 and 25 mM) at 24 h and 5 min exposure times. Biofilms were viewed using Live-Dead Baclight stain and confocal scanning laser microscopy and quantified using the software COMSTAT2.ResultsAt 3 and 60 mg/mL, ISMN-ULV liposomes had comparable and significant anti-biofilm effects compared to untreated control at 24 h exposure (p = 0.012 and 0.02 respectively). ULV blanks also had significant anti-biofilm effects at both 24 h and 5 min exposure (p = 0.02 and 0.047 respectively). At 5 min exposure, 60 mg/mL ISMN-MLV liposomes appeared to have greater anti-biofilm effects compared to pure ISMN or ULV particles. Increasing liposomal lipid content improved the anti-biofilm efficacy of both MLV and ULVs at 5 min exposure.ConclusionLiposome-encapsulated “nitric oxide” is highly effective in eradicating S. aureus biofilms in-vitro, giving great promise for use in the clinical setting to treat this burdensome infection. Further studies however are needed to assess its safety and efficacy in-vivo before clinical translation is attempted.

Role of melatonin and the nitric oxide donor ISMN in a model of brain ischemic-hypobaric hypoxia

Nitric oxide (NO) is a versatile diffusible signaling molecule with physiological actions involved in neuromodulation, immune response, and vasodilatation. In addition, NO appears to be key in brain hypoxic or ischemic injury. Many studies have demonstrated a neuroprotective effect for melatonin based on its antioxidant activity. In this fashion, we have optimized an experimental model of ischemia followed by a hypobaric hypoxia (I + HH) period associated to co-administration of NO donor isosorbide mononitrate (ISMN) and melatonin, in order to study: (1) the localization and activity of iNOS and eNOS, and protein nitration in the brain of rats submitted to the above mentioned model after two reoxygenation periods (0 and 2 h) and (2) the effect of the administration of both drugs in the brain of rats submitted to this hypoxic model after the same reoxygenation periods. Our results show that the co-administration of ISMN and melatonin induces an increase of eNOS vascular localization after ischemia-hypoxia while it does not influence iNOS in situ expression. Regarding NO activity measured as NADPH-diaphorase histochemistry, it is remarkable that at the 0 h point, no signal was detected. On the other hand, protein nitration-related damage in both reoxygenation times is decreased when both drugs are supplied. In summary, ISMN and melatonin co-administration induces the main changes observed in the parameters analyzed after ischemia-hypoxia. Supported by MICINN (SAF2008-03938).

Effects of co-administration of the nitric oxide donor ISMN and melatonin in the NO system in a model of hypobaric hypoxia

Nitric oxide (NO) is a molecule that depending both on its concentration and tissue redox status, can develop a dual neuroprotective/neurotoxic function. In this sense, it has been demonstrated: (1) that NO plays a crucial role in hypoxic situations and, (2) that antioxidants can exert neuroprotective effects by alleviating the negative consequences derived from the reactive oxygen species (ROS) generated in the hypobaric process, and related to NO as well. Nevertheless, only few studies have analyzed the effect of co-administration of NO donors and antioxidants on brain hypoxia. Thus, we have optimized an experimental model of hypobaric hypoxia (HH) that resembles high altitude environmental conditions in order to study the NO system response to this situation. In this study we analyze the localization and activity of iNOS and eNOS, and protein nitration in the brain of rats submitted to the above mentioned model after two reoxygenation periods (0 and 2 h). Moreover, we studied the effect of co-administration of NO donor isosorbide mononitrate (ISMN) and the neurohormone melatonin in this hypoxic model. Our results show that the co-administration of ISMN and melatonin does not influence iNOS in situ expression, but decreases eNOS after the 2 reoxygenation periods, as well as NO activity (measured as NADPH-diaphorase staining). On the other hand, protein nitration-related damage at 2 reoxygenation times is decreased when both drugs are supplied. In summary, the co-administration of ISMN and melatonin in our model of hypoxia seems to modulate the NO system response. Supported by MICINN (SAF2008-03938).

A comparative study between isosorbide mononitrate (IMN) versus misoprostol prior to hysteroscopy

Abstract Objective To compare the efficacy of a nitric oxide donor (isosorbide mononitrate) and a prostaglandin E1 analogue (misoprostol) for cervical priming before hysteroscopy. Design Comparative clinical trial. Methods A total of 162 patients with diagnosed intrauterine lesions scheduled for hysteroscopy were allocated to two groups: in group A patients ( n =81) IMN 40mg was inserted into the posterior fornix of the vagina while misoprostol 200μg was inserted into the posterior fornix of the vagina in group B patients ( n =81). Results There was no significant difference between IMN and misoprostol with regard to the duration of application or difficult dilatation. In contrast, there was a significant difference between IMN and misoprostol with regard to baseline cervical dilatation (5mm for IMN and 8mm for misoprostol) and duration of dilatation (73s for IMN and 49s for misoprostol). There was no significant difference between IMN and misoprostol with regard to nausea, vomiting and hot flushes. In contrast, there was a significant difference between IMN and misoprostol with regard to abdominal pain (17 cases for IMN and 55 cases for misoprostol) and headache (65 cases for IMN and 9 cases for misoprostol). Conclusion Misoprostol is superior to isosorbide mononitrate regarding better baseline cervical dilatation, less duration of dilatation, less incidence cervical injury and finally better feasibility of the procedure.

Cervical priming in the first trimester: morphological and biochemical effects of misoprostol and isosorbide mononitrate

To evaluate morphological changes and inflammatory events in the uterine cervix following presurgical treatment with the prostaglandin analogue misoprostol or the nitric oxide donor isosorbide mononitrate (IMN). Experimental study. Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION OF SAMPLE: Primigravid women (n=32) scheduled for surgical termination of first trimester pregnancy, treated vaginally overnight with either misoprostol (200 microg), IMN (40 mg) or no treatment (controls). Before evacuation, cervical biopsies were obtained with the use of a Tru-Cut biopsy needle. Morphology was studied by electron microscopy. For assessment of inflammatory events the expression of the matrix metalloproteinases MMP-1 and MMP-9 was estimated by immunohistochemistry and interleukin IL-8 was quantified by ELISA. Misoprostol induced splitting and disorganization of the collagen fibres. Compared to specimens from women who had received no treatment, the granular endoplasmatic reticulum appeared enriched and dilated and the nuclear chromatin was clearly dispersed. Similar changes of a lesser degree were observed in specimens obtained from IMN-treated women. Staining intensity for MMP-1 and MMP-9 was more evident in specimens obtained from IMN-treated women compared to women who had received treatment with misoprostol or no treatment. The levels of IL-8 were higher following treatment with misoprostol compared to IMN and controls. The study demonstrates that misoprostol as well as IMN induces morphological changes and inflammatory events of the cervix. Changes of the collagen network were more pronounced in samples obtained from women treated with misoprostol compared to IMN.

Outpatient cervical ripening with nitric oxide donor isosorbide mononitrate prior to induction of labor

Objective: To examine the effectiveness and safety of outpatient vaginal administration of isosorbide mononitrate (IMN) to induce cervical ripening. Methods: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted on 102 singleton term pregnant women with unfavorable cervices who were randomly assigned to receive outpatient intravaginal IMN or placebo before admission for induction of labor. The main outcome variable was time from hospital admission to delivery. Secondary outcomes included fetal and maternal morbidity, labor characteristics, and incidence of cesarean delivery. Results: The admission–delivery interval was 13.45±6.63 and 20.12±8.19 h (P=0.0001) for the IMN and placebo groups, respectively. Of the IMN patients 62.75% needed prostaglandins for cervical ripening versus 90.2% with placebo (P=0.002). The incidence of tachysystole was significantly lower in the IMN group (P<0.05) but there were no significant differences in cesarean delivery rate, neonatal outcomes, and incidence of hyperstimulation. Conclusions: Outpatient use of IMN resulted in shorter admission to delivery interval, and was associated with less prostaglandin use and lower incidence of uterine tachysystole.

Nitric oxide donor isosorbide mononitrate for pre‐induction cervical ripening at 41 weeks' gestation: A randomized controlled trial

Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to determine whether sustained release isosorbide mononitrate (ISMN-SR) 60 mg administered vaginally is effective for pre induction cervical ripening at 41 weeks' gestation. A double-blind randomised controlled trial was carried out at the University Obstetric Unit, Galle, Sri Lanka for a period of 9 months, commencing 1st August 2003. One hundred and fifty-six consecutive women with uncomplicated singleton pregnancies at 41 weeks' gestation with a modified Bishop Score <5 were allocated by stratified (primip/multip) block randomization to receive either ISMN-SR 60 mg (n = 78) or vitamin C 100 mg (n = 78) vaginally. Modified Bishop Score at 41 weeks + 2 days' gestation and the proportions establishing spontaneous labor or becoming favorable for induction of labor (IOL) by 41 weeks + 2 days' gestation were evaluated in each group. At the commencement of the study there were no differences between the mean age, parity or modified Bishop Score of the two groups. In the ISMN-SR group, there was a marked increase in the proportion establishing spontaneous labor (28% vs 7.5%, P < 0.01) and being favorable for IOL (40% vs 9% P < 0.001), 2 days after therapy. In the ISMN-SR group, there was a significantly higher increase in the mean modified Bishop Score (3.8, 95% CI 2.3-5.3 vs 1.3, 95% CI 0.3-2.2, P < 0.01) and a marked decrease in the proportion of subjects requiring further ripening of the cervix with a Foley catheter. (32% vs 79%, P < 0.001). The cesarean section rates were similar in both groups. Sustained release ISMN administered vaginally is effective for preinduction cervical ripening.

Outpatient vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening and labor induction postterm: a randomized controlled study

Our aim was to examine the efficacy, safety, and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting. Two hundred pregnant women of at least 42 weeks' gestation with an unripe cervix were randomly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets. Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group (P < .05). In women who did not go into labor, cervical status was similar in the 2 groups the next day. Headache was a common side effect. No maternal or fetal side effects of clinical importance were registered. Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective, safe, and well tolerated procedure. The definitive clinical efficacy and safety needs to be evaluated in larger series of patients.

The “PRIM” study: A randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term

The “PRIM” study: A randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term

Isosorbide mononitrate induces increased cervical expression of cyclooxygenase-2, but not of cyclooxygenase-1, at term

Objective Prostaglandin and nitric oxide (NO) are both known to be involved in cervical ripening at term. The aim of the study was to investigate if NO has an effect on cervical expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the two main isoenzymes involved in prostaglandin synthesis, and to localize these enzymes within the cervix. Study design Women with an unripe cervix scheduled for elective caesarean section at term were randomly selected to receive vaginally either the NO donor isosorbide mononitrate (IMN) or placebo 4 h before surgery. At the operating theatre, cervical tissue specimens were obtained for immunoblotting and immunohistochemistry. Results Increased expression of COX-2 was found in specimens exposed to IMN compared to specimens obtained from women in the placebo group. There was no difference in the expression of COX-1. Immunohistochemistry revealed similar localization of the two enzymes in treated and untreated women. Conclusions Vaginal administration of IMN induces increased cervical expression of COX-2, but not of COX-1. This pathway may be of importance in the process of cervical ripening at term.

The “PRIM” study: A randomized comparison of prostaglandin E 2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term

The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term. Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening. Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group. Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.

The “prim” study+a randomised comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening prior to the induction of labour at term

The “prim” study+a randomised comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening prior to the induction of labour at term

Inhibition of Vascular Oxidative Stress in Hypercholesterolemia by Eccentric Isosorbide Mononitrate

We sought to determine if the nitric oxide (NO) donor isosorbide mononitrate (ISMN) (200 mg/kg body weight/day) decreases vascular bioavailability of superoxide in atherosclerosis. Vascular oxidative stress limits the bioavailability of endothelial NO and promotes atherosclerosis, while NO itself exerts antioxidative effects. It is unknown if therapeutic NO impacts on vascular oxidative stress in atherosclerosis. New Zealand white rabbits (n = 10 each group) were fed either normal chow (control), cholesterol chow (CHOL) (0.75%), or cholesterol chow enriched with ISMN (CHOL-ISMN). Rabbits were fed twice daily. After 16 weeks we used aortic segments to measure vascular superoxide (5-microM lucigenin), intimal lesion formation, and vasoreactivity to acetylcholine (ACH) and ISMN. Plasma cholesterol increased by 40-fold in CHOL and CHOL-ISMN. The plasma concentration of ISMN in CHOL-ISMN was 1,529 +/- 447 ng/ml. Superoxide formation (control: 228 +/- 20 counts/20 min/mg) was strongly enhanced in CHOL (345 +/- 46 counts/20 min/mg, p = 0.02) but not in CHOL-ISMN (229 +/- 23 counts/20 min/mg) demonstrating antioxidative effects of eccentric ISMN in vivo. In parallel, intima-media thickness of thoracic aorta (159 +/- 4 microm in control) was reduced from 645 +/- 41 microm (CHOL) to 440 +/- 51 microm (CHOL-ISMN, p < 0.05). Likewise, eccentric ISMN partially restored vascular responses to the NO donor S-nitroso-N-acetyl-D,L-penicillamine and improved endothelium-dependent vasorelaxation. The maximal ACH relaxation increased from 26.3 +/- 9.6% in CHOL to 49.7 +/- 8.1% in CHOL-ISMN; ISMN treatment induced a moderate nitrate tolerance as evidenced by diminished ISMN-induced vasodilation. These data suggest that eccentric ISMN can completely inhibit the increase of vascular bioavailability of superoxide and partially prevent intimal lesion formation and endothelial dysfunction in hypercholesterolemia.

Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study

Objective Our aim was to examine the effect of the nitric oxide donor isosorbide mononitrate on the uterine cervix at term and to evaluate possible adverse effects of this treatment. Study design Term pregnant women were randomly selected to receive either 40 mg vaginally administered isosorbide mononitrate or placebo 4 hours before elective cesarean section. Cervical status, maternal blood pressure, maternal pulse rate, fetal heart rate, umbilical arterial Doppler indices, and various side effects were examined. Results Isosorbide mononitrate induced a significant increase in cervical distensibility. It also caused a significant change in maternal blood pressure and maternal pulse rate. In addition, the frequency of maternal headache and palpitations was significantly higher in the isosorbide mononitrate group versus the placebo group. However, the intensity of these symptoms was moderate. Conclusion Vaginal administration of 40 mg of isosorbide mononitrate induces cervical ripening at term. Although the majority of women experienced side effects, no serious clinical maternal or fetal adverse effects, resulting in specific medication or emergency cesarean section, were diagnosed.

Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: A randomized controlled trial to determine effects on maternal and fetal hemodynamics

Objective: Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term. Study Design: We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes. Results: Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination–only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination–only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination–only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index. Conclusions: Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant. (Am J Obstet Gynecol 2001;184:958-64.)

A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening: a randomised controlled trial

Objective To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400μg) for pre-operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone. Design Randomised controlled trial. Setting Glasgow Royal Infirmary. Population Sixty-six primigravid women scheduled for suction termination of pregnancy. Methods Women were randomly assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg ( n=22), misoprostol 400 μg ( n=22) or both agents together [isosorbide mononitrate 40 mg and misoprostol 400 μg] ( n=22). Main outcome measures 1. To assess the cumulative force required to dilate the cervix to 8 mm; 2. the onset of new symptoms before termination of pregnancy. Results The cervical resistance following combination therapy with isosorbide mononitrate and misoprostol was not significantly different than following misoprostol alone [24.5N vs 18.5N; median difference (95% CI) 19N (-22 to 49)]. Pre-treatment with misoprostol used alone resulted in a lower cervical resistance than isosorbide mononitrate alone (18.5 N vs 39 N, P=0.04, Mann-Whitney U test). There was no difference in the number of women remaining asymptomatic following either isosorbide mononitrate or misoprostol or combination therapy [14/22 (64%) vs 11/21 (52%) vs 11/22 (50%), Fisher's exact test]. Conclusions We have not shown any advantage of combining misoprostol with the nitric oxide donor isosorbide mononitrate compared with misoprostol alone for pre-operative cervical ripening in the first trimester.